DESCRIPTION (Applicant?s Abstract): Stem cells derived from bone marrow can be injected into recipient animals and engraft in various nonhematopoietic tissues including muscle, cartilage, bone, brain, and liver, as fully differentiated parenchymal cells. Injected marrow-derived stem cells are also detectable in the lung tissue of these recipients but little is known about the origin or fate of these cells. This grant proposal presents initial work demonstrating that cultured marrow stromal stem cells can be intravenously injected into recipient mice and reproducibly detected in recipient lung tissue as cells of type I pneumocyte morphology. As marrow stromal cells are a heterogeneous population of several cell subtypes, whether one or all of these subtypes can serve as alveolar epithelial precursors is not known. Furthermore, whether this process can be facilitated by altering alveolar epithelial turnover or by exposure to factors that affect cell phenotype is not clear. Building upon initial observations, this grant proposes, first, to identify and purify the bone marrow stem cell subtype able to form alveolar epithelium in vivo, and, second, to augment the ability of bone marrow stem cells to incorporate into alveolar epithelium by priming the stem cells or the alveolar epithelium prior to stem cell infusion. The findings in these experiments would be used to plan future work evaluating the use of marrow stromal stem cells as rescue therapy in diseases affecting the alveolar epithelium.